Many studies have shown that brain stem regions such as the nucleus raphe magnus and periaqueductal gray can control the inflow of sensory information to the spinal cord. It has recently been found that selective analgesia may result from stimulating these brain stem centers and that morphine analgesia may be mediated by the same mechanisms. Pathways implicated in this "descending control" extend from enkephalin-containing neurons in the mesencephalic central gray which project to serotonergic neurons in the n. raphe magnus which in turn project to the spinal cord marginal zone (MZ) (lamina 1), substantia gelatinosa (SG) (lamina 2) and nucleus proprius (lamina 5). However, many questions still remain unanswered, including 1) the involvement of other, as yet unknown pathways from the brain stem to the spinal cord; 2) the types of neurotransmitters involved at each central nervous sytem (CNS) level; and 3) the morphological and physiological substrates by which these descending pathways produce their effects at spinal levels. This research proposal is aimed at providing information on these issues by studying: 1) the spinal terminations of physiologically identified brain stem neurons at the light & EM levels; 2) the synaptic conductance changes evoked by focal brain-stem stimulation endings of primary and second order neurons of known transmitter content and physiological activity; 3) the types of neurotransmitters released by brain stem neurons; 4) the effects of anesthetics and the decerebrate state on the responses of MZ and SG neurons. Histochemical and radioactive tracers will be used to identify pathway for light & EM examination. Conventional single unit recordings, both extra and intracellular, will be used for physiological demonstrations. Iontophoresis of intracellular labels will be used to identify the recorded neurons at both light and EM levels. Finally, immunocytochemistry, combined with anatomical tracers, will be used to establish the relationship of descending connections to the various putative neurotransmitters found in the spinal SG. The results of these studies should lead to a basic understanding of the mechanisms whereby the CNS can modulate somato-sensory information at the spinal level.